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The Link between Mental Health and Gut Health

The ‘root cause’ of mental health conditions like anxiety and depression are multi-factorial. Genetics, socioeconomic status, early childhood experiences, history of traumatic brain injury, self-beliefs, self-esteem, etc. are all involved. I don’t want to suggest or imply that gut health is the only driving force that predisposes or aggravates an existing mental health condition…but it’s certainly a big one. Until recently, its role has been completely disregarded.

If you recall from my last post (review here), our gut and brain are in constant communication with each other. Our gut has an entire nervous system, composed of ~100 million nerves and these connect directly to the base of the brain. These nerves have receptors that respond to the presence (structural components) of bacteria and the metabolites that the bacteria release.

Intestinal Hyperpermeability a.k.a Leaky Gut Syndrome

Normally, the cells that line our gastrointestinal (GI) tract are tightly connected to neighbouring cells to prevent the passage of unwanted material. You can think of it like a brick wall – it’s the physical divide between our external environment (like the food we eat) with our internal environment. The only difference is that our GI tract is dynamic and not a static structure, so in the presence of large dietary proteins, it becomes more permeable, creating spaces in between neighbouring cells to allow them to pass through.

Our microbiome can be in a dysbiotic state (either lack of ‘good’ bacteria and/or too many ‘bad’ bacteria) by a variety of factors that have been previously discussed (read here.) Dysbiotic bacteria trigger a more permeable (‘leaky’) gut wall, so more space is made between neighbouring cells along the GI tract. This allows bacteria, bacterial metabolites, and food fragments to enter our systemic circulation. These things shouldn’t be in our internal environment, so as a consequence, our immune system mounts a response and this can create a variety of undesirable symptoms and underlie various conditions. (This mechanism is hypothesized to be the driving force behind autoimmune disease.)


The BBB is a cluster of blood vessels just outside of our brain that is highly selective on which molecules can pass through. It’s similar to our GI lining – it acts as a physical barrier keeping things out that shouldn’t be there.

In the context of mental health:

1. Some dysbiotic bacteria secrete inflammatory metabolites like TNF-alpha and MCP, which can access the BBB via the gut-brain axis and make the BBB more permeable (leaky). Their technical name is cytokines, and there are tons of different cytokines that elicit various immune responses. The new-found access of cytokines, bacteria, etc. within the brain triggers an inflammatory response, altering neuron function, and ultimately, brain function. This has been linked to conditions like anxiety, depression, and cognitive decline. This mechanism supports the theory that chronic inflammation underlies mental health conditions vs. ‘chemical’ imbalances.

Read Resource #4 to read a study on how this was demonstrated in humans

2. Hypothalamus Pituitary Adrenal (HPA) Axis Dysfunction – This axis is the pathway of the stress response, starting with signals being generated in the brain (perception of stress) and ending with cortisol being secreted from the adrenal glands. A stress response isn’t always a bad thing – it’s actually anti-inflammatory, helps with athletic performance, prevents procrastination, etc. It’s more of a problem when it’s activated too often, leading to HPA dysfunction and altered stress responses. In research, HPA axis dysfunction is considered a reliable biological ‘readout’ of anxiety and depression - as in, it's very common.

Link to gut? Pro-inflammatory cytokines that arise from the gut can travel to brain, make BBB more leaky, gain access, and trigger the hypothalamus to start the stress-response cascade. The bacteria are the instigators!

3. Serotonin: This is our happy, feel good neurotransmitter. Conventional anti-depressants target serotonin by preventing the re-uptake so that more is left around for our neurons. Most people are surprised to learn that ~90% of serotonin is produced in the gut by cells that line the GI tract. Serotonin production can be impaired when these cells are physically damaged by dysbiosis and consequential local inflammation. Again, it comes back to the integrity of the GI lining.